Bevacizumab With or Without Surgery for Adult Glioblastomas

Phase 2

Withdrawn

• Conditions: Glioblastoma; Brain Neoplasm

• Registration Number: NCT01413438
• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Brief Summary

Background:

- Glioblastoma (GBM) is the most common malignant brain tumor in adults. Patients with GBM are usually treated with surgery, radiation, and chemotherapy. Despite this treatment, most GBMs start growing again. Bevacizumab, a chemotherapy drug, has shown promise in slowing the growth of GBMs. More research is needed to find out whether having surgery before starting bevacizumab is more effective than bevacizumab alone.

Objectives:

- To compare surgery plus bevacizumab to bevacizumab alone in adults with glioblastoma.

Eligibility:

- Individuals at least 18 years old whose glioblastoma has come back after treatment.

Design:

* All participants will be screened with a physical exam, medical history, blood tests, and imaging studies.

* Participants will be divided into two groups. One group will have surgery followed by bevacizumab. The other group will have the drug without surgery.

* The first group will have surgery as soon as possible and will begin bevacizumab 4 weeks after surgery. The second group will start the drug as soon as possible.

* Both groups will receive the drug as an infusion every 2 weeks. They will be monitored with frequent blood tests and imaging studies. The infusions will continue for as long as the drug is effective at preventing tumor regrowth.

* Participants will be contacted every 4 weeks after they stop taking bevacizumab. They will answer followup questions either in person or by telephone.

Detailed Description

Objective

The objective of this prospective randomized controlled study is to determine the overall survival benefit of tumor resection in patients with recurrent glioblastoma multiforme (GBM).

Study Population

This study will recruit 42 adults with a diagnosis of recurrent grade 4 astrocytoma into each of two arms, for a total of 84 patients. All participants will be good candidates for elective surgical resection of their tumors according to the previously established NIH Recurrent Glioma Scale (NRGS), which uses performance status, tumor volume, and tumor involvement of critical/eloquent brain areas as prognostic criteria. Patients who require biopsy only or have previously been treated with bevacizumab will be excluded.

Design

Participants will be stratified by NRGS score (NRGS 0 or NRGS 1-2) and randomized to surgery followed by bevacizumab or to bevacizumab alone. Patients assigned to the surgical arm will undergo their procedure within 28 days of randomization. Treatment with bevacizumab at a dose of 10 mg/kg every 2 weeks will begin at least 28 days later to allow adequate craniotomy wound healing. Patients assigned to the non-surgical arm will start bevacizumab at a dose of 10 mg/kg every 2 weeks immediately. MRI evaluations will take place within 72 hours of surgery to assess extent of resection, 28 days postoperatively, 96 hours after starting bevacizumab, and then every 28 days until tumor progression is documented. Follow-up assessments will take place every 28 days while on bevacizumab until tumor progression. Once progression is established, patients will be free to pursue further surgical and/or medical salvage therapy as they wish. Patients will be followed until their time of death.

Outcome Measures

The primary outcome measure is median overall survival from the date bevacizumab is started. Secondary outcome measures include the rate of progression-free survival 6 months after starting bevacizumab, median progression-free survival, overall survival rates at 6 and 12 months after starting bevacizumab, objective response rate, health-related quality of life, change in KPS of 20 points or more, time to need for additional tumor therapy, and use of corticosteroids.

Study Timeline

• Study Start: 2011-07-15
• Study First Submitted: 2011-08-09
• Study First Submitted QC: 2011-08-09
• Study First Posted: 2011-08-10
• Status Verified: 2013-09-26
• Primary Completion: 2013-09-26
• Study Completion: 2013-09-26
• Last Update Submitted: 2017-06-30
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Median Overall Survival	2 years

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) at 6 months & median PFS in each arm, objective response rate by the RANO criteria (OR), and overall survival rate at 6 and 12 months in each arm, compare rate of change in health-related quality of life.	2 years